Characterising knotting properties of polymers in nanochannels.

Using a lattice model of polymers in a tube, we define one way to characterise different configurations of a given knot as either "local" or "non-local", based on a standard approach for measuring the "size" of a knot within a knotted polymer chain. The method involves associating knot-types to subarcs of the chain, and then identifying a knotted subarc with minimal arclength; this arclength is then the knot-size. If the resulting knot-size is small relative to the whole length of the chain, then the knot is considered to be localised or "local"; otherwise, it is "non-local". Using this definition, we establish that all but exponentially few sufficiently long self-avoiding polygons (closed chains) in a tubular sublattice of the simple cubic lattice are "non-locally" knotted. This is shown to also hold for the case when the same polygons are subject to an external tensile force, as well as in the extreme case when they are as compact as possible (no empty lattice sites). We also provide numerical evidence for small tube sizes that at equilibrium non-local knotting is more likely than local knotting, regardless of the strength of the stretching or compressing force. The relevance of these results to other models and recent experiments involving DNA knots is also discussed.

Handlebody decompositions of three-manifolds and polycontinuous patterns.

We introduce the concept of a handlebody decomposition of a three-manifold, a generalization of a Heegaard splitting, or a trisection. We show that two handlebody decompositions of a closed orientable three-manifold are stably equivalent. As an application to materials science, we consider a mathematical model of polycontinuous patterns and discuss a topological study of microphase separation of a block copolymer melt.

Anxiety relaxation during MRI with a patient-friendly audiovisual system.

INTRODUCTION: Many patients experience anxiety, not limited to claustrophobia, before magnetic resonance imaging (MRI) examination. We performed a non-randomized controlled trial to evaluate whether a patient-friendly audiovisual (AV) system in the MR scanner room reduces patient anxiety. METHODS: We randomly selected 61 participants from outpatients who required brain MRI examination. Patients were informed that they could choose to undergo an MRI examination with a patient-friendly AV system (Ambient Experience, Philips Healthcare, Best, The Netherlands) or the standard system. To complete the MRI examination without affecting clinical practice, all patients who preferred the patient-friendly AV system were assigned to the preferring AV group. Patients who indicated that either system was acceptable were randomly assigned to the no preference but allocated AV group or control (using the standard system) groups. In both groups, state anxiety using the State-Trait Anxiety Inventory (STAI) was assessed before and after the MRI examination (A-State-before and A-State-after MRI, respectively). The changes in A-State-before and A-State-after MRI were categorized as follows: relieved high-state anxiety, no change in high-state anxiety, stable easiness, and intensified anxiety. RESULTS: Among the 61 included patients, 19 were assigned to the preferring AV group, 20 to the no preference but allocated AV group, and 22 to the control group. There were no significant differences between the group. However, in patients with high-state anxiety before MRI, the preferring AV group and the no preference but allocated AV group, which used the patient-friendly AV system, relieved high-state anxiety by 63.6% (7 of 11 patients) and 81.8% (9 of 11 patients), respectively. In contrast, the control group using the standard system relieved high-level anxiety by only 42.9% (three out of seven patients). CONCLUSION: The patient-friendly AV system may reduce anxiety in patients undergoing MRI examinations. IMPLICATIONS FOR PRACTICE: The patient-friendly AV system may reduce anxiety in patients undergoing MRI examination by providing a more patient-centered MRI examination environment. These findings may help ameliorate negative perceptions associated with MRI examination.

Ethylene formation from ethyl moiety of ethionine.

In plants, ethylene is formed in the presence of light and flavin mononucleotide from ethionine and S-ethylcysteine. The ethylene is formed from the ethyl moiety of ethionine.

Polynucleotides. XXVIII. Stimulation of the binding of aminoacyl-tRNA to ribosomes by tri- and polynucleotide analogs.

Messenger activity of synthetic tri- and polynucleotide analogs was studied by binding of 14C-labeled aminoacyl-tRNAs to ribosomes in the presence of the analogs. Synthetic messengers used were: poly(A) analogs in which adenosine was replaced by tubercidine (I), 3-deazaadenosine (II), 1-deazaadenosine (III) and 2-methyladenosine (IV); copolymers of adenosine and aristeromycin (V); cyclic triadenylate (VI); the heptanucleotide of 6,2'-O-cyclouridine (VII); the pentanucleotide of 8,2'-S-cycloadenosine (VIIIa); A-U-G analogs in which adenosine was replaced by 8,2'-O- and S-cycloadenosine (VIII), 8,5'-O- and S-cycloadenosine (IX); 8-oxyadenosine (x); 8-bromoadenosine (XI) and formycine (XII). Among these oligo- and polynucleotides, analogs which contained nucleotides of anti conformation having appropriate bases for Watson-Crick type hydrogen bonding stimulated the binding of corresponding tRNAs to ribosomes.

Sequence variations of the glucokinase gene in Japanese subjects with NIDDM.

Mutations in the glucokinase gene have been identified recently in patients with maturity-onset diabetes of the young, a subtype of NIDDM. The proposed role of glucokinase as a glucose sensor, combined with the low insulin response to glucose found in most Japanese with NIDDM, prompted us to speculate that mutations in the glucokinase gene might be one of the major causes of NIDDM in Japanese subjects. To determine the prevalence of mutations and sequence variations in the glucokinase gene, we screened all 12 exons of the glucokinase gene, including exon/intron junctions, by polymerase chain reaction followed by single-strand conformation polymorphism in 209 Japanese NIDDM subjects. In addition to the mutation in exon 7, which substituted Arg (AGG) for Gly (GGG) at codon 261 (10), a silent mutation of Pro (CCC-->CCG) in exon 4 at codon 145 and several new sequence variations in intervening sequences and the 5'-untranslated region of exon 1 beta (beta-cell-specific exon 1) were identified. Because we identified only one subject who had a structurally abnormal glucokinase molecule, we conclude that the prevalence of structural mutations in the glucokinase gene responsible for NIDDM appears to be rare among Japanese patients. To our knowledge, this is the first thorough study describing the ethnic prevalence of mutations and sequence variations in the glucokinase gene in NIDDM.

Intraoral minor salivary gland tumors: a clinicopathological study of 82 cases.

We present a retrospective study of 82 patients with intraoral minor salivary gland tumors which were diagnosed from 1979 to 2003 in Gifu University Hospital. The histological diagnoses were reevaluated according to the 1991 WHO classification. A total of 82 tumors, consisting of 55 benign and 27 malignant tumors, were found in 28 male and 54 female Japanese patients; the male-to-female ratio was 1:1.9. The mean age of the patients was 51.4+/-18.1 years. The tumors affected the palate (n = 64), the buccal region (n = 10), the upper lip (n = 6), the floor of the mouth (n = 1), and the retromolar region (n = 1). Histologically, the tumors were classified as pleomorphic adenoma (n = 54), papillary cystadenoma (n = 1), adenoid cystic carcinoma (n = 10), mucoepidermoid carcinoma (n = 8), acinic cell carcinoma (n = 3), adenocarcinoma (n = 2), basal cell adenocarcinoma (n = 1), papillary cystadenocarcinoma (n = 1), and carcinoma in pleomorphic adenoma (n = 2). From the results of the present study and review of the literature, it is suggested that the minor salivary gland tumors in Japan may be characterized by a higher incidence of benign tumors, especially of pleomorphic adenoma; a more marked tendency for female predominance; a higher incidence of palatal involvement; and a rarer occurrence of polymorphous low grade adenocarcinoma, in comparison with those reported in the literature from outside of Japan.

The high prevalence of the diabetic patients with a mutation in the mitochondrial gene in Japan.

Recently, an A to G transition at position 3243 in transfer ribonucleic acidLeu(UUR) [the 3243 base-pair (bp) mutation] originally found in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes has been identified in patients with diabetes and deafness. To determine the prevalence of the diabetic patients with this mutation in Japan, we screened 550 randomly selected cohorts of diabetic patients without prior information about clinical features such as type of diabetes, family history of diabetes, age of onset, and mode of therapy. We have identified 5 patients with this mutation, suggesting that approximately 0.9% of diabetic patients have the 3243 bp mutation. However, there were no subjects with this mutation in 250 controls with normal glucose tolerance. The percentage of mutant DNA in whole mitochondrial DNA did not correlate to the degree of symptoms. We conclude that the 3243 bp mutation in the mitochondrial gene plays an important part as a cause of diabetes in Japan.

Analysis of the glucokinase gene promoter in Japanese subjects with noninsulin-dependent diabetes mellitus.

Glucokinase plays an important role in glucose metabolism in pancreatic beta-cells and liver. Recently, several mutations responsible for noninsulin-dependent diabetes mellitus (NIDDM) have been identified within the coding regions of the glucokinase gene. We screened the promoter regions using polymerase chain reaction followed by single strand conformation polymorphisms in 240 Japanese NIDDM and 111 control subjects. In the beta-cell promoter, two kinds of sequence variations were detected. One variation, in which 2 nucleotides at position -282 (C-->T) plus -194 (A-->G) were changed simultaneously, was found in 23 NIDDM (9.6%) and 12 control (10.8%) subjects. The other variation [e.g. -30 (G-->A)] was identified in 87 NIDDM (36.3%) and 40 control (36.0%) subjects. In the liver promoter, in addition to the -603 (G-->T) substitution in 1 NIDDM (0.4%) and 2 control (1.8%) subjects, the -120 (G-->T) substitution in 1 control (0.9%) subject was found. However, there were no differences in these allele frequencies between NIDDM and control subjects. We conclude that the prevalence of mutations in the promoter of the glucokinase gene responsible for NIDDM is rare among Japanese patients.

A fluorinated 2-nitroimidazole, KU-2285, as a new hypoxic cell radiosensitizer.

To develop new hypoxic cell radiosensitizers, we incorporated fluorine atoms into the side chain of the 2-nitroimidazole. Of the resulting compounds, KU-2285 (a 2-nitroimidazole with an N1-substituent of CH2CF2CONHCH2-CH2OH) was considered the most useful as a hypoxic cell radiosensitizer. In this study, its in vivo radiosensitizing activity and acute toxicity were compared with those of etanidazole. The reduction potentials of KU-2285 and etanidazole were -0.96 V and -1.05 V vs Ag/Ag+ in N,N-dimethylformamide, respectively, and their respective octanol/water partition coefficients were 0.25 and 0.040. The in vivo radiosensitizing activity of KU-2285 was found to be similar to that of etanidazole at the same administration dose when assayed by an in vivo-in vitro assay, a growth delay assay, and a tumor control assay using SCC VII tumor or transplanted mammary tumor in C3H/He mice. Although the radiosensitizing activity of etanidazole was reduced when it was administered orally, there was no significant difference in the radiosensitizing activity of KU-2285 whether it was administered intravenously, intraperitoneally, or orally. The acute toxicity measured as the LD50/7 in 8-week-old female C3H/HeJ mice was found to be 2.4 g/kg (intravenously), 2.1 g/kg (intraperitonealy), and 4.25 g/kg (orally) for KU-2285, whereas it was 4.75 g/kg (intravenously) for etanidazole.

Characteristics of fluorinated nitroazoles as hypoxic cell radiosensitizers.

Types of 2-nitroimidazoles and 3-nitro-1,2,4-triazoles bearing one or two fluorine atoms on their side chains were synthesized to evaluate their physicochemical properties, radiosensitizing effects, and toxicity. The reduction potential of the compounds containing one fluorine was similar to that of misonidazole (MISO), whereas that of the difluorinated compounds was slightly higher. Both mono- and difluorinated compounds had an in vitro sensitizing activity comparable to or slightly higher than that of MISO. The fluorinated 3-nitrotriazoles were almost as efficient as the 2-nitroimidazoles with the same substituent. In vivo, some of the compounds were up to twice more efficient than MISO, whereas others were as efficient as MISO. Toxicity in terms of LD50/7 in mice was quite variable depending on the side-chain structure; the amide derivatives were less toxic than MISO, whereas the alcohol and ether derivatives were more toxic. In view of the radiosensitizing effect and toxicity in vivo, at least one compound, KU-2285 (a 2-nitroimidazole with an N1-substituent of: CH2CF2CONHCH2CH2OH) has been found to be as useful a hypoxic cell sensitizer as SR-2508.

Immunolocalization of lipoprotein(a) in wounded tissues.

Fifty samples from inflamed tissues were examined by immunohistochemical techniques, using antibodies against apo(a), apo B, plasminogen, fibrinogen, proliferating cell nuclear antigen (PCNA), and various components of extracellular matrix. The immunohistochemical features of granulation tissues were characterized by different stages of wound healing. In the first stage, immunoreactivities for anti-apo(a) and anti-apo B were weak and focal, whereas those for anti-plasminogen and anti-fibrinogen were strong and were widespread on the tissue surface. In the second stage, granulation tissues were covered with loose fibrous connective tissue, designated as a "fibrous cap." In this stage, markedly positive staining for lipoprotein(a) [Lp(a)] was observed closer to the surface of the fibrous cap than plasminogen, suggesting that Lp(a) may prevent external fibrinolysis. Lp(a) was also found in endothelial cells and the extracellular space of small vessels underlying the fibrous cap. In the last stage of healing, apo(a) and apo B were not detectable in completely organized tissues. These findings suggest that Lp(a) plays a role in the wound healing.

Endotracheal/endobronchial metastases : clinicopathologic study with special reference to developmental modes.

BACKGROUND: Endotracheal/endobronchial metastases (EEMs) from nonpulmonary neoplasms are rare. However, their definition and developmental modes have not yet been fully elucidated. METHODS: EEMs were defined as documented nonpulmonary neoplasms metastatic to the subsegmental or more proximal central bronchus, in a bronchoscopically visible range. The clinical and pathologic features of 16 cases were reviewed, with special emphasis on the developmental modes based on five criteria: location in the tracheobronchial tree, number of lesions, laterality of lesions, depth of lesions, and relationship with the associated bronchus. RESULTS: The developmental modes were proposed on the basis of the above five criteria as follows: type I, direct metastasis to the bronchus; type II, bronchial invasion by a parenchymal lesion; type III, bronchial invasion by mediastinal or hilar lymph node metastasis; and type IV, peripheral lesions extended along the proximal bronchus. Primary tumors included colorectal in six patients, breast in three patients, uterus in two patients, osteosarcoma of the bone in two patients, and maxillary, larynx, and parotid carcinoma in one patient each, respectively. The mean recurrence interval was 65.3 months. The developmental modes were as follows: type I, five patients; type II, one patient; type III, four patients; and type IV, nine patients. Three patients underwent surgical resection. One patient has remained well for 5 years after operation. Median and mean survival times were 9 months and 15.5 months, respectively. CONCLUSION: The mean recurrence interval was long at 65.3 months, but the mean survival time was short at 15.5 months. Type I accounted for only 5 of 16 patients. Type II was found in only one patient. It is thought that this type is a rare form. Type IV affected nine patients. Treatment plans must be individualized, because in some cases, long-term survival can be expected.

The ultrastructure of the retina in adult metachromatic leukodystrophy.

A 46-year-old woman afflicted with biochemically proven metachromatic leukodystrophy had only mild optic atrophy shortly before her death. Repeated earlier ophthalmoscopic examinations had not revealed any retinal abnormalities. Light microscopy of the retina showed strong acid phosphatase activity in both enlarged ganglionic cells and pigment epithelial cells. Demyelination of both optic nerves was not noted. Ultrastructurally, membranous lysosomal residual bodies were confined to ganglionic cells. We found lipofuscin material in pigment epithelial cells, but also within metachromatic leukodystrophy-specific residual bodies of ganglionic cells. The presence of lipofuscin represents the "wear-and-tear" phenomenon, possibly enhanced by the metachromatic leukodystrophy.

Intrahepatic cholangiocarcinoma arising 10 years after the excision of congenital extrahepatic biliary dilation.

A 52-year-old woman was found to have a liver tumor during treatment for a liver abscess. The tumor was diagnosed as intrahepatic cholangiocarcinoma by closer examinations, including a percutaneous needle biopsy. Ten years previously, she had undergone excision of a choledochal cyst, with reconstruction by Roux-en-Y hepaticojejunostomy, as treatment for Todani's type Ia congenital biliary dilation, which had been confined only to the extrahepatic bile duct. The significant association between congenital biliary dilation and hepatobiliary malignancies is well known. Some patients have been reported to develop biliary cancer long after the excision of the entire extrahepatic bile duct and hepaticoenterostomy. However, in these patients, the development mostly took place in the remnant choledochal cyst, the anastomotic site, or in the dilated intrahepatic bile duct of Todani's type IV-A congenital biliary dilation. The development of intrahepatic cholangiocarcinoma after operation has not been reported previously in a patient with Todani's type I congenital biliary dilation. This case suggests that the entire biliary tree may have a high risk of field cancerization, even in extrahepatic congenital biliary dilation.

Usefulness of MR imaging in the postsurgical monitoring of gallbladder cancer in a patient with bile duct cancer that developed 7 years after resection of mucinous adenocarcinoma of the gallbladder.

We encountered a case of left hepatic duct cancer that developed 7 years after surgical resection of early-stage adenocarcinoma of the gallbladder. A 65-year-old woman was hospitalized with high fever and general fatigue. She also had elevated serum levels of alkaline phosphatase, gamma-glutamyltranspeptidase, and carbohydrate antigen 19-9. Seven years earlier, she had undergone extended cholecystectomy and resection of the extrahepatic bile duct for early-stage mucinous adenocarcinoma of the gallbladder. Conventional examinations did not reveal any responsible lesions. Magnetic resonance (MR) cholangiography, however, showed a tumor obstructing the left hepatic duct, and dynamic MR images revealed multiple foci of bacterial abscess in the liver. Surgically resected tissue again revealed mucinous adenocarcinoma. The present case is rare in that metachronous mucinous adenocarcinoma of the biliary system occurred after a long interval. This case suggests the usefulness of MR imaging in the postsurgical monitoring of patients with gallbladder carcinoma.

Enzyme-linked immunosorbent assay of lipoprotein(a) in serum and cord blood.

We have developed a new sensitive method for quantifying lipoprotein(a) (Lp(a] in human serum, using a 'sandwich' type noncompetitive enzyme-linked immunosorbent assay (ELISA). The solid-phase used was a polystyrene plate. The anti-Lp(a) antibody-enzyme conjugate was labelled by linking Fab' fragments to peroxidase (EC 1.11.1.7) by the maleimide method. The minimum detectable concentration was 0.5 ng/well. Routinely, the assay was carried out with 1,000-fold diluted serum, and Lp(a) was quantified between 4.0 and 500 mg/l. Within-run coefficients of variation (CVs) ranged from 3.5% to 10.4% and between-run CVs from 5.0% to 11.1%. Results by the ELISA were in good agreement with those by radial immunodiffusion (r = 0.955). The distribution of Lp(a) in serum from 820 healthy donors was highly skewed: mean 141.1 mg/l, medium 97.9 mg/l. In cord blood, the mean and median were 15.6 and 9.8 mg/l, respectively. This ELISA for Lp(a) has the advantages of being highly sensitive and specific, simple to perform, and does not use radioisotopes.

Some properties of a capillary permeability-increasing enzyme-2 from the venom of Agkistrodon caliginosus (Kankoku-Mamushi).

Capillary permeability-increasing enzyme-2 (CPI-enzyme-2) consists of a single polypeptide chain with an isoelectric point of pH 3.5. The enzyme is composed of 369 amino acid residues, based on a mol. wt of 44,000, and contains 20.3% carbohydrate. Both arginine ester hydrolytic and capillary permeability-increasing activities of the enzyme were inhibited by treatment with diisopropylfluorophosphate, indicating that the enzyme is a serine proteinase. The N-terminal amino acid sequence shows homology with that of CPI-enzyme-1 and similarity to those of batroxobin or kallikrein-like enzyme from other snake venoms.

Purification of a capillary permeability-increasing enzyme-2 from the venom of Agkistrodon caliginosus (Kankoku-Mamushi).

A capillary permeability-increasing enzyme-2 was purified from the venom of A. caliginosus by ion-exchange chromatography and gel filtration on Sephadex G-100. By this procedure, 3.1 mg of purified enzyme was obtained from 4 g of the venom. The mol. wt of the purified enzyme was estimated to be approximately 44,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme hydrolyzed N-alpha-tosyl-L-arginine methylester with a specific activity of 56.5 units/mg of protein, and did not show any caseinolytic, clotting or bradykinin-releasing activity. When 13.9 micrograms of the enzyme was injected into the depilated skin on the back of a rabbit, capillary permeability was increased.

Comparative study of fibrinogen degradation by four arginine ester hydrolases from the venom of Agkistrodon caliginosus (Kankoku-Mamushi).

When purified capillary permeability-increasing (CPI)-enzyme-1, CPI-enzyme-2, kininogenase-1 or kininogenase-2 was incubated with human fibrinogen at a ratio of 1:100 by weight, a loss of fibrinogen coagulability was seen at prolonged incubation times. CPI-enzyme-2 and kininogenase-1 caused a rapid loss of coagulability, while CPI-enzyme-1 and kininogenase-2 acted more slowly. When human fibrinogen and each enzyme were incubated at 37 degrees C, CPI-enzyme-2 first cleaved the A alpha-chain then the B beta-chain. The action of CPI-enzyme-1 was similar, but slower. Kininogenase-1 initially caused slow degradation of the B beta-chain than the A alpha-chain, while kininogenase-2 only caused slow cleavage of the A alpha-chain. Although these enzymes did not show thrombin-like activity, CPI-enzyme-2 was able to release fibrinopeptide B faster than fibrinopeptide A, while kininogenase-1 only released fibrinopeptide A. These results indicate that these enzymes differ in their ability to degrade human fibrinogen.